Emerging clinical research in hypomyelinating leukodystrophies (HLD) necessitates definition of surrogate markers as endpoints in possible clinical trials. Standardized assessment of myelination using myelin sensitive MRI is therefore highly desirable. Proposed protocols comprise DTI, MT-imaging and myelin water imaging employing the mcDESPOT sequence. We report first experiences applying mcDEPSOT in patients with cerebral folate deficiency. Myelin water fraction (MWF) allowed assessment of subtle gradual and regional changes with sufficient spatial resolution. The extent of the myelin deficit in diffuse hypomyelination can more reliably be evaluated using the MWF parameter. McDESPOT seems a feasible, system independent method to study pediatric HLD.